rs121907939
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PM4_SupportingPP5_Moderate
The NM_000152.5(GAA):c.2707_2709del(p.Lys903del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,018 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. Q902Q) has been classified as Likely benign.
Frequency
Consequence
NM_000152.5 inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GAA | NM_000152.5 | c.2707_2709del | p.Lys903del | inframe_deletion | 19/20 | ENST00000302262.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GAA | ENST00000302262.8 | c.2707_2709del | p.Lys903del | inframe_deletion | 19/20 | 1 | NM_000152.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461018Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 726808
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Glycogen storage disease type II, infantile Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Apr 01, 1995 | - - |
Glycogen storage disease, type II Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 27, 2023 | This variant has been observed in individual(s) with clinical features of Pompe disease (PMID: 7717400; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This variant, c.2707_2709del, results in the deletion of 1 amino acid(s) of the GAA protein (p.Lys903del), but otherwise preserves the integrity of the reading frame. ClinVar contains an entry for this variant (Variation ID: 4028). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this variant affects GAA function (PMID: 7717400, 21972175). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at